Abstract: This grant application requests resumption of the funding, that was interrupted for one year because of the departure of the previous principal investigator. The clinical studies are designed to improve the survival of children with cancer through multidisciplinary randomized, collaborative treatment protocols that are stratified to the patients stage of disease and their prognostic groups. Whenever possible the treatments are reduced to minimize both short and long term toxicity. Epidemiologic studies are conducted to study the incidence, natural history and possible courses of childhood malignancies. Laboratory studies will be conducted to study the biology of cancer cells and correlate these with the clinical variables. The aims of our participation and those of CCSG are a) to provide large numbers of patients for Groupwide studies in order to make multiarm, randomized, prospective studies possible, b) to utilize the scientific leadership, expertise and clinical experience of Pediatric Oncologists at MSKCC to help design and implement new studies, and c) to contribute administrative expertise and experience to Standing Committees of CCSG. Clinical studies will continue in the evaluation and development of new chemotherapeutic agents for patients who become refractory to conventional therapy. Pharmacologic studies will evaluate drug metabolism and correlate it with therapeutic response. Studies will be conducted in the role of bone marrow transplantation in hematopoietic disorders. The extensive clinical facilities of MSKCC with the well developed intensive supportive care program and its research laboratories will make it possible to develop novel treatment protocols. They will be piloted on the large patient population and made available for groupwide randomized prospective trials. The clinical personnel of MSKCC have extensive and proven experience in the design and implementation of innovative treatment protocols that have been adopted worldwide. They will continue to provide leadership for CCSG in study committees and strategy groups. Members of the affiliate hospitals have been participating in CCSG studies and have proven their ability to conduct the clinical studies and they provide material for the laboratory evaluation.